Project Summary Alzheimer's Disease and Related Dementias (ADRD) have long challenged clinicians, researchers, and policymakers as the only leading causes of death in the United States without disease-modifying treatment. One of the most common and potent risk factor is the ?4 allele of the apolipoprotein E gene, APOE, which has been the focus of intense research and lay public interest. While APOE?4 (?APOE?) is associated with an increased risk for late-onset AD, on its own it has not been found to have clinical validity and utility. Thus, clinical guidelines recommend against APOE testing, either direct-to-consumer (DTC) or clinician ordered. In 2017, despite the lack of clinical guidelines recommending APOE testing, the FDA approved 23andMe's Genetic Health Risk Report, which includes testing for APOE as well as other conditions and studies have shown that a majority of consumers' value APOE testing and state they would like to obtain it. The dynamic surrounding APOE testing, including consumer access to testing despite the lack of known clinical utility and with results provided to consumers outside of the clinical care context ? represents an overarching challenge that we believe will increasingly become a clinical, economic, and policy conundrum. The objective of this supplement will be to develop conceptual frameworks and methodological approaches to examine the economic, financial/coverage, and policy implications of genetic testing for ADRD risk and conduct initial analyses in the following areas: (1) Coverage policies for ADRD genetic testing (2) Role of physicians in managing patients who present their APOE DTC testing results (3) Economic value of ADRD genetic testing The particular focus of this Supplement is APOE testing for late-onset AD because of its availability via DTC testing. However, we will place this work into the larger context of testing for other ADRD risk factors and thus consider a range of genetic risk variants, dementia types (e.g., frontotemporal dementia, Lewy Body Dementia), and forms of disease (early- vs. late-onset; familial vs. sporadic).